Bioengineered liver models screen drugs and study liver injury

Yet another bioengineered liver model is based on perfusion systems or bioreactors that enable dynamic fluid flow for nutrient and waste exchange. These so called liver-on-a-chip devices contain hepatocyte aggregates adhered to collagen-coated microchannel walls; these are then perfused at optimal flow rates both to meet the oxygen demands of the hepatocytes and deliver low shear stress to the cells that’s similar to what would be the case in vivo. Layered architectures can be created with single-chamber or multichamber, microfluidic device designs that can sustain cell functionality for 2-4 weeks.

Some of the limitations of perfusion systems include the potential binding of drugs to tubing and materials used, large dead volume requiring higher quantities of novel compounds for the treatment of cell cultures, low throughput, and washing away of built-up beneficial molecules with perfusion.

The ongoing development of more sophisticated engineering tools for manipulating cells in culture will lead to continued advances in bioengineered livers that will show improving sensitivity for the prediction of clinically relevant drug and disease outcomes.

This work was funded by National Institutes of Health grants. The author Dr. Khetani disclosed a conflict of interest with Ascendance Biotechnology, which has licensed the micropatterned coculture and related systems from Massachusetts Institute of Technology, Cambridge, and Colorado State University, Fort Collins, for commercial distribution. Dr. Underhill disclosed no conflicts.

SOURCE: Underhill GH and Khetani SR. Cell Molec Gastro Hepatol. 2017. doi: org/10.1016/j.jcmgh.2017.11.012.